In the present specification the spatial configuration of the substituents related to the chiral carbon atom denoted with ".alpha." is characterized by "S" and "R", respectively. The designations "cis" and "trans", respectively, mark the position of the substituents attached to carbon atom "3" of the cyclopropane ring related to the spatial configuration of the substituents of carbon atom "1". The absolute spatial configuration of the substituent attached to carbon atom "1" is denoted with the prefix "1R" and "1S", respectively.
In the present specification the various enantiomers and enantiomer-pairs are designated with the following abbreviations:
Ia: mixture of 1RcisS and 1ScisR PA1 Ib: mixture of 1RtransS and 1StransR PA1 Ic: mixture of 1RcisR and 1ScisS PA1 Id: mixture of 1RtransR and 1StransS PA1 If: 1RcisS PA1 Ig: 1RtransS PA1 Ih: 1ScisR PA1 Ii: 1StransR PA1 a/ preparing a saturated solution from a mixture comprising the desired isomers in admixture with further possible isomers with a protic or apolar aprotic inert organic solvent, seeding the solution with a seeding crystal consisting of the enantiomer-pair 1RtransS+1StransR and isolating the precipitated crystals at a temperature between +30.degree. C. and -30.degree. C.; or PA1 b/ seeding a melt of a mixture comprising the desired isomers in admixture with further possible isomers at a temperature between 10.degree. C. and 60.degree. C. with a seeding crystal consisting of the 1RtransS++1StransR enantiomer-pair, crystallizing at a temperature between 30.degree. C. and -10.degree. C., and if desired suspending the mixture thus obtained in a protic or apolar aprotic organic solvent at a temperature between -10.degree. C. and -20.degree. C. and isolating the separated crystals; or PA1 c/ subjecting a mixture comprising the desired isomer-pair Ib in admixture with further possible isomers to chromatography in an organic solvent preferably on a silica gel or Kieselguhr adsorbent; or PA1 d/ dissolving a mixture comprising trans isomers of the compounds of the Formula /I/ in a protic or apolar aprotic solvent, seeding the solution with a seeding crystal consisting of the enantiomer-pair 1RtransS+1StransR /Ib/, isolating the precipitated crystalline product Ib, and thereafter if desired epimerising the mixture comprising Ib+Id being present in the mother-lye with an organic or inorganic base and if desired repeating the said step and/or the crystallizing step; or PA1 e/ dissolving the mixture comprising the trans isomers in a secondary or tertiary organic amine base comprising 4-9 carbon atoms--optionally by adding an organic solvent--and seeding the solution thus obtained with a seeding crystal consisting of 1RtransS+1StransR isomers and thereafter isolating the precipitated crystals.
It is known that pyrethroids of the Formula /I/ (known under the generic name "cypermethrin") belong to the valuable family of synthetic pyrethroids and are useful as insecticide (Hungarian patent No. 170,866). These compounds may be prepared by reacting m-phenoxy-benzaldehyde cyanohydrine with the corresponding cyclopropane carboxylic acid chloride in the presence of a base [Pestic. Sci. 6,537, . . . 1975]. The product thus obtained consists of eight stereoisomers i.e. of a mixture of four enantiomer-pairs. If a 60:40 mixture of the corresponding trans and cis cyclopropane carboxylic acid chlorides is used, the mixture contains 18-19% of enantiomer-pair Ia, 21-22% of enantiomer-pair Ic, 26-27% of enantiomer-pair Ib and 33-34% of enantiomer-pair Id.
According to prior art the stereoisomers of cypermethrin show different biological activity. It is generally accepted that the activity of molecules comprising cis cyclopropane carboxylic acids is superior to that of the corresponding trans derivatives [Pest. Sci. 7, 273, 1976].
In the comparative biological tests of various pyrethroids [Pest. Sci. 9, 112-116, 1978] the cis and trans stereoisomers--including the cypermethrin stereoisomer-pairs--were evaluated together.
The comparative tests were carried out on Musca domestica L. and Phaedon cochleariae Fab species. Concerning the chloro derivatives from the trans isomers activity data of 1RtransS (Ig) and 1RtransR were disclosed. The said data show that--while the 1RtransS isomer possesses a strong activity--the 1RtransR isomer is considerably less active [according to the test the activity related to bioresmetrine (100) amounts to 1400 and 81, respectively, on Musca domestica and to 2200 and 110, respectively, on Phaedon cochleariae]. It was disclosed further that the activity of a mixture of both tested isomers was lower than the calculated value. Thus the isomers showed an antagonism rather than the expected synergism and the rate of antagonism amounted to 1.42 and 1.46 on house fly and mustard beetle, respectively.
As a result of the said tests and publications the trans isomers and mixtures thereof were pushed to the background of biological interest and research was focused to active cis derivatives and mixtures thereof. This lead to the development of alphamethrin (isomer mixture of 1RcisS and 1ScisR (Ia) of the chloro derivatives) and decamethrin [comprising the 1RcisS isomer (If) of the bromo derivatives].
Similar data were set forth for the bromo derivative; on mustard beetle the rate of antagonism amounts to 1 48.